Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with alpha tricalcium phosphate

  1. Myat Nyan1,2,3,*,
  2. Takayuki Miyahara1,2,
  3. Kanako Noritake1,2,
  4. Jia Hao1,2,
  5. Reena Rodriguez1,2,
  6. Shinji Kuroda1,
  7. Shohei Kasugai1,2

Article first published online: 18 DEC 2009

DOI: 10.1002/jbm.b.31559

Issue

Journal of Biomedical Materials Research Part B: Applied Biomaterials

Journal of Biomedical Materials Research Part B: Applied Biomaterials

Volume 93B, Issue 1, pages 65–73, April 2010

Additional Information

How to Cite

Nyan, M., Miyahara, T., Noritake, K., Hao, J., Rodriguez, R., Kuroda, S. and Kasugai, S. (2010), Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with alpha tricalcium phosphate. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 93B: 65–73. doi: 10.1002/jbm.b.31559

Author Information

  1. 1

    Department of Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Tokyo, Japan

  2. 2

    Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan

  3. 3

    Department of Prosthodontics, University of Dental Medicine, Yangon, Myanmar

*Department of Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Publication History

  1. Issue published online: 4 MAR 2010
  2. Article first published online: 18 DEC 2009
  3. Manuscript Accepted: 27 SEP 2009
  4. Manuscript Revised: 20 AUG 2009
  5. Manuscript Received: 29 MAY 2009

Funded by

  • Global Center of Excellence Program
  • International Research Center for Molecular Science in Tooth and Bone Diseases
  • Tokyo Medical and Dental University, Tokyo, Japan

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Keywords:

  • bone healing;
  • simvastatin;
  • alpha tricalcium phosphate;
  • BMP-2;
  • TGF-β;
  • bone formation

Abstract

We have previously reported that healing of rat calvarial defects was enhanced by application of alpha tricalcium phosphate (αTCP) combined with simvastatin, a cholesterol synthesis inhibitor. The purpose of the present study was to investigate the cellular and molecular mechanisms in this phenomenon. Rat calvarial defects were grafted with αTCP with or without simvastatin or left untreated. Animals were sacrificed on 3, 7, 10, 14, and 21 days postoperatively and histological changes in the defect region were assessed. Gene expression patterns were examined by RT-PCR. Proliferation and migration of osteoprogenitor cells from the dura mater were increased in simvastatin group from day 3 to day 10 (p < 0.01). New bone formation was significantly increased in simvastatin group on day 14 and day 21 (p < 0.01). BMP-2 expression was significantly higher in simvastatin group on day 3 and day 14 (p < 0.05) and maintained until day 21. Increased upregulation of TGF-β1 was also observed in the simvastatin group on day 7 (p < 0.05) which was maintained until day 14. These findings suggest that the proliferation and recruitment of osteoprogenitor cells were critical steps in early stage of bone healing and that these steps were enhanced by TGF-β1 and BMP-2, which were stimulated by simvastatin. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010

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